Nephropathology V. Žampachová I. ÚP Anatomical remarks nVessels - 90% of blood flow through the cortex nAfferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillary plexus (from superficial glomeruli) or vasa recta for medulla (from juxtamedullary glomeruli) nterminal arteries nglomerular damage commonly leads to damage of peritubular blood flow – risk of ischemia Possible clinical signs nWeight gain, edema – fluid retention nThirst – chronic renal failure, DM nFatigue – acute/chronic renal failure (RF) nFever – urinary tract infection (UTI) nHeadache – hypertension, RF nHematuria – UTI, glomerulonephritis, tumor, stone nPolyuria – DM, tubular disorders nRenal diseases commonly clinically silent! Clinical features nDiminished renal reserve – GFR ~ 50% of normal nRenal insufficiency - GFR 20-50% of normal nAzotemia – increase of blood urea and creatinine due to decreased glomerular filtration (20-30%), or extrarenal cause n Uraemia - azotemia together with several clinical and biochemical abnormities: metabolic, endocrine, … nuremic gastroenteritis/colitis + IS dysregulation, malnutrition; nhypertension, fibrinous pericarditis, AS acceleration npneumonia, pleuritis ndermatitis, itching nrenal osteodystrophy, osteoporosis, muscle loss nperipheral neuropathy, Clinical features nRenal failure - GFR less than 20-25%, oedema, uraemia; causes: prerenal, postrenal, renal (vascular, glomerular, tubulointerstitial); acute r.f. (oliguria→anuria) chronic r.f. nEnd-stage renal disease - GFR less than 5% of norm nAnuria <100ml/24hrs Clinical features nNephritic syndrome due to acute glomerular disease; hematuria + mild proteinuria + hypertension; oliguria + azotemia + mineral dysbalance nRapidly progressive glomerulonephritis – very rapid (days - a few weeks) nephritic syndrome nNephrotic syndrome: usually chronic gl. dis., severe proteinuria (>3,5 g/d) + hypoalbuminemia/oedema + hyperlipidemia + lipiduria; possible ↑ infections (IgG loss) n Clinical features nAsymptomatic hematuria and/or proteinuria – commonly mild glomerular lesion nPolyuria + nocturia + electrolyte disorders – renal tubular defects nBacteriuria + pyuria – urinary tract infection (UTI) nRenal colic + hematuria - nephrolithiasis Renal diseases n congenital anomalies n glomerular diseases n vascular diseases ntubulointerstitial diseases n tumors Congenital anomalies n10% of all people nhereditary or acquired developmental defect ndecreased volume of renal tissue (e.g. agenesis) ndisorders of differentiation (dysplasia) nanatomical abnormalities (ectopy) nmetabolic disorders (cystinuria) Agenesis nBilateral agenesis – 1:6000, incompatible with independent life, usually stillborn, accompanied by characteristic appearance (Potter‘s syndrome), commonly associated with other congenital defects nUnilateral agenesis – infrequent, the opposite kidney enlarged by compensatory hypertrophy n Oligohydramnion (Potter´s syndrome) ndecreased amount of amniotic fluid (placental abnormities, renal agenesis or malformation) nflat face, lung hypoplasia, limb deformities, ... Potter copy Hypoplasia n n nAbnormally small kidneys (x atrophy) nreduced number of lobes and pyramids hypoplsieledviny Renal ectopy nAbnormal site, usually in pelvis, due to migration stop of the metanephros nA. renalis - from lower aorta or a. ilica communis nShort ureter Ren migrans, ren mobilis nNot a malformation, normal a. renalis nSecondary renal descensus, usually due to loss of adipous capsule nLong ureter, risk of obstruction and infection Horseshoe kidney nRenal pole fusion nUreteral obstruction podkovledv Cystic renal disease nHereditary, congenital nonhereditary, acquired nPathogenesis: primary defect of tubular epithelial cells and their growth, resulting in tubular dilatation nSecondary tubular obstruction (oxalate crystals etc.) nMultiple or solitary nAffects the whole kidney, or mostly cortex or medulla Cystic dysplasia nUni- or bilateral nEnlarged multicystic kidney nCysts mm-cm. nIslands of undifferentiated mesenchyme, immature tubules nCommonly cartilage nBilateral - renal insufficiency dysplasieledviny dysplasieledviny copy Polycystic kidney - autosomal recessive nInfants nEnlarged kidney at birth, smooth surface, microcystic nRadial elongated cysts and channels nCongenital hepatic fibrosis nRF in childhood dětskápolycystickanemoc copy apckd Adult polycystic kidney disease (APKD) Autosomal-dominant, liver cysts, berry aneurysms. 1:500-1:1000. Pain, hematuria, UTI, stones, hypertension, slow progression, chronic RF at 40-60 yrs. ↑risk of ca copy Adult polycystic kidney n Simple cyst nSingle or multiple nUp to 10 cm nHaemorrhage posible nDifferential diagnosis x cystic tumors n„Complicated“ cyst – with regressive changes, diff. dg. x ca Cystaprostá Renal biopsy imf2 Untitled1 ~LWF0002 Direct immunofluorescence Electron microscopy Normal glomerulus schemaglom copy Glomerular filtration barrier Glomerular diseases nClassification by aetiology and mechanisms of injury (primary x secondary; immunological x non-immunological) nHistological classification (patterns of injury – proliferative, membranous change, membrano-proliferative, crescentic, hyalinisation + sclerosis) nOne disease may have variable morphology/pattern (SLE) nOne pattern may be seen in variable disorders n Glomerular diseases nNephritic syndrome, rapidly progressive GN: inflammation +/- endothelial damage; ↑ gl. cellularity nusually immune mediated nImmune complex deposition (acute proliferative GN, SLE) nAntibodies x glomerular basement membrane (Goodpasture sy) nSystemic noninfectious vasculitis: autoantibodies p-ANCA, c-ANCA; (polyangiitis with granuloma) nimmune mediated abnormalities of complement system regulation (C3) n n Glomerular diseases nNephrotic syndrome: malfunction/leakage of barrier-filtration system - ↑ increased permeability nCapillary wall: thickening by in situ IC deposits (membranous glomerulopathy; primary, sec.), abnormal substances (DM, amyloid) nEpithelial cells: loss of normal structure (detachment + loss of podocytes, compensatory hypetrophy of remaining cells, fusion of foot processes in minimal change disease; disruption in focal segmental glomerulosclerosis) n Glomerular diseases nNon-immune mediated lesions nvascular n hemodynamic factors n hypertension n ischemia Patterns of glomerular injury nProliferative – increased glomerular cellularity, combination of endogenous proliferation and exogen. infiltration nMembranous change – thickening of loops due to BM expansion + IC deposition nMembrano-proliferative nCrescentic – florid prolif. of cells in Bowman‘s capsule + infiltration, later fibrotic changes nHyalinisation – extracellular/intramural amorphous material w. plasmatic proteins + lipids, PAS+, silver impregnation - nSclerosis – extracellular collagenous matrix, membranes, PAS+, impregn. + n Glomerular injury distribution n nDiffuse – almost all glomeruli affected (> 50- 80%) nFocal – only some glomeruli nGlobal – affecting the whole glomerulus nSegmental – affecting only part of the glomerulus n IC localisation n n n n n n schemadepositglom Mesangial Subepithelial Subendothelial Epimembranous copy Progression in glomerular disease n↓ GFR (30-50% of normal) → independent progression to RF – ablation nephropathy nFocal segmental glomerulosclerosis – adaptation – compensatory glomerular hypertrophy (glomerular + systemic hypertension → proteinuria → mesangial proliferation + matrix accumulation → sclerosis) nTubulointerstitial fibrosis – proteinuria + ischemia → tubular damage + interstitial inflammation Clinical presentations nIsolated proteinuria nsometimes asymptomatic nglomerular – damage to filtration membrane nselective – proteins w. low-middle molecular weight (albumin) nnonselective – more damage, high weight proteins – Ig ntubular nproblem in tubular resorption of LMW proteins nIsolated hematuria nmicroscopic x macroscopic Clinical presentations nNephritic syndrome – acute gl. damage, rapid start, hematuria, variable proteinuria, oliguria, edema, hypertension, azotemia, mineral dysbalance nNephrotic syndrome - heavy proteinuria > 3,5 g/daily, generalised edema, hypoalbuminemia, hyperlipidemia, lipiduria; hypercoagulative state (loss of coagulation proteins, increase in blood viscosity) Clinical presentations nAcute renal failure – progressive oliguria to anuria, azotemia, metabolic acidosis; nprerenal – renal – postrenal nwith according therapy usually return to function nChronic renal failure - prolongated symptoms of uremia, anemia, nausea nchronic uremia in irreversible damage nmost commonly due to DM, hypertension, AS GLOMERULAR DISEASES nPRIMARY GLOMERULAR DISEASE: kidney as a main affected organ, other clinical signs due to impaired renal function (i.e. minimal change disease) nSECONDARY GLOMERULAR DISEASE: renal injury only a part of systemic disease affecting multiple organs (lung, joints, skin), i.e. SLE NORMGLOMHE AKGNHE RPGNSRPKY IgAHEIMF fsgs2 ~AUT0001 mpgnhe FokGN 12slegnafog amyloid ChronsklerotisujíciGN chrongn chrongn Chronic sclerosing GN Normal kidney GN Glomerulopathy nOne histological type may have variable clinical presentation, i.e. membranoproliferative lesion may present as glomerulonephritis with nephritic sy, glomerulopathy with nephrotic sy, or isolated hematuria Glomerulopathy with: nProteinuria or nephrotic syndrome nIsolated or predominant hematuria nHematuria + proteinuria combined w. renal failure nGlomerulopathy due to vascular diseases nGlomerulopathy in systemic lupus nChronic glomerulopathy Glomerulopathy with proteinuria or nephrotic syndrome nMinimal glomerular change disease nFocal segmental glomerulosclerosis nMembranous glomerulopathy nAmyloidosis nDiabetic nephropathy Minimal change disease nMost common cause of nephrotic sy in children nheavy selective proteinuria - albuminuria nmostly in children ≤ 5 yrs nin adults commonly associated w. NSAID, ML nLight microscopy + IMF normal nGenetic predisposition + immunological basis (association with respiratory infection, atopy, Hodgkin lymphoma) nEpithelial cell injury – effaced foot processes nSteroid therapy, good prognosis in children, in adults necessity of biopsy – dif. dg. Minimal change disease PAS1.jpg Minimal change disease Loss of epithelial foot processes in elmi, fat in tubular epithelia („lipoid nephrosis“) n NORMGLOMHE MGZ copy Focal segmental glomerulosclerosis nNephrotic sy, ↑ incidence, any age nHematuria, ↓ GFR, proteinuria nProgression usual – 50% → RF in 7 years, steroid-resistant nPrimary nidiopathic, n variable podocyte protein mutations, plasma factor ↑ permeability (soluble urokinase receptor?),apolipoprotein L1 mutations (black African descent) nSecondary: late part of adaptive response to preexisting renal disease (renal ablation - reflux nephropathy, hypertension, glomerulopathies – IgA, SLE,…) nAssociation with other diseases (HIV, obesity, toxins – heroin, drugs) n FSGS nepithelial damage nhyalinosis (plasma protein leakage), foamy macrophages nsegmental sclerosis (mesangial matrix production, capillary loops collapse) nNo immune deposits on IF nPodocyte injury on EM n n Focal segmental glomerulosclerosis fsgs2 Membranous glomerulopathy nprimary autoimmune, nmostly older adults – most common nephrotic sy in this age group nAb x specific receptor in podocytic membrane antigen – phospholipase A2 receptor nproteinuria or nephrotic sy, variable course, 1/3 RF ndiffuse global glomerulopathy nthickening of capillary wall, subepithelial IC deposits, „spikes“ - BM material in impregnation nno increased glomerulus cellularity Membranous glomerulopathy nsecondary – infections (HBV, HCV, syphilis, malaria) tumors (lung ca, colorectal ca, melanoma), drugs (NSAID), nautoimmune diseases (SLE, thyroiditis) n ! older patients may have both tumor AND autoimmune MGN ~AUT0002 ~AUT0001 mgnimf Membranous glomerulopathy copy Diabetes mellitus and kidneys nNonenzymatic glycosylation of proteins – accumulation of irreversible glycosylation products in BM of vessel walls, metabolic defect – increased collagen synthesis, hemodynamic changes nDiabetic microangiopathy in kidney (glomerulosclerosis) and retina (diabetic retinopathy). Diffuse thickening of capillary BM leads to ischemic changes, simultaneously increased plasmatic proteins permeability Diabetic nephropathy nDiabetic microvascular disease nClinically: non-nephrotic proteinuria, nephrotic syndrome, chronic renal failure nMorphology: glomerulosclerosis (diffuse mesangial, nodular), hyalinizing arteriolar sclerosis, tubulointerstitial lesions (steatosis and glycogenation of tubular epithelium, pyelonephritis, papillary necrosis) nthe most common causes of chronic RF n40 % of diabetics will have nephropathy n n n Diabetic glomerulosclerosis nDiffuse glomerulosclerosis – GBM thickening, increase in mesangial matrix + cellularity nNodular glomerulosclerosis - (Kimmelstiel-Wilson) after 10-15 yrs; PAS+ nodular acellular material deposits at the tips of capillary loops; leads to chronic renal insufficiency nno immune deposits in IMF Diabetic glomerulosclerosis Diabetic glomerulosclerosis Diabetic glomerulosclerosis nFurther renal complications in diabetics naccelerated arteriolosclerosis and arteriosclerosis, hypertension nPyelonephritis nRenal papillary necrosis in acute PN DiabetGS Diaibetes Diabetic glomerulosclerosis Renal amyloidosis nAmyloidosis – pathologic deposits of abnormal microfibrillary (8-10nm) proteinaceous acellular material nEosinophilic in HE, Kongo red +, green dichroism in polarised light nFirm pale enlarged kidney in macroscopy Renal amyloidosis nAmyloid deposits in glomerular mesangial matrix and capillary walls; glomerular obliteration nPeritubular and blood vessel walls nProteinuria nNephrotic syndrome nCHRI amyloid Glomerulopathy with hematuria nPrimary: IgA nephropathy (Berger‘s disease) n Alport syndrome / thin basement membranes sy nSecondary (systemic): some types of SLE n Henoch-Schönlein purpura n IgA nephropathy nRecurrent hematuria, children and young adults w. genetic predisposition, after GIT, respitatory tract, urinary tract infections, may → RF; most common cause of RF in primary glomerulopathies nvariable course nIgA and C3 mesangial deposition, mesang. cells and matrix proliferation, segmental glomerulosclerosis nAbnormal increase/pathologic form of IgA production, AAxIgA – IC;↓ clearance of IC in cirrhosis IgAHEIMF copy IgA nephropathy n nchanges of IgA nephropathy present in Henoch-Schönlein purpura – IgA vasculitis npreexisting respiratory infection npurpura due to vasculitis w. IgA deposits (+ skin rash, GIT hemorrhage, arthritis) nin children regeneration, in adults possible RF copy Alport syndrome nPart of collagen IV glomerulopathies ngenetic disorder, 90% X-linked, AR or AD nabnormal basement membranes (lamina densa), later FSGS, tubular atrophy, interstitial fibrosis nmanifestation mostly in kidney (hematuria – nefritis, proteinuria), RF; nHD, transplantation near – deafness neye – lens + cornea disorders, cataract n n Thin basement membrane nbenign familial hematuria, no progression to RF ncommon inherited lesion – hereditary nephropathy nheterozygous carriers of collagen IV mutations or less dangerous collagen IV mutations nwithout other problems (ocular, …) ndifferential diagnosis Glomerulopathy w. acute nephritic sy nproliferative GN w. increased mesangial/ endocapillary cellularity, commonly crescentic nacute (diffuse endocapillary) proliferative GN nmembranoproliferative GN (C3, prim. IC), nrapidly progressive GN nsecondary mostly in vasculitis – SLE, n microscopic polyangiitis n granulomatosis with polyangiitis (Wegener) n n n n n Diffuse proliferative GN npostinfectious (str., staph., viruses, protozoan - malaria, toxoplasmosis; schistosomiasis) nin systemic disorders (inf. endocarditis, necrotising arteritis nany age, nformerly children more commonly, after strep. nnow adults after staph. (+ DM, alcohol, age) nacute nephritis (+ fever, nausea) nmay be partially crescentic (→ progressive) nprognosis – regeneration usual in children, in adults possible ↓ renal function Diffuse proliferative GN nvariable signs: hematuria, proteinuria, hypertension, edemas, renal insufficiency npossible without signs ncapillary stenosis, increased endocapillary and mesangial cellularity nIMF: granular deposits in capillary loops and mesangium – IgG, C3 nEM: subepithelial, mesangial deposits - humps Diffuse proliferative GN AKGNHE Diffuse proliferative GN subepithelial immune complex deposition, postinfective AKGNEMHUMPS akgnimf Elmi „humps“ Immunofluorescence copy granular deposits Membranoproliferative GN nformerly type I-III MPGN nNow: a group of disorders w. complement abnormalities nC3 part of complement present in biopsy, dysregulation, inflammation nImmune complexes GN ninflammatory diseases w. proliferative GN, IMF IgG+, C3+ nIC: cryoglobulinemia (80% due to HCV); SLE, HIV; malignancy (CLL, ML), alpha1- AT deficiency), nC3 nephropathy (C3 GN and dense deposit disease) n young, poor progn., CHRI, recurrent in graft n Membranoproliferative GN ndiffuse mesangial + endothelial cells activation and proliferation (mesangiocapillary GN), mesangial matrix expansion, BM thickening – „duplication – tram-track“ mpgnhe Rapidly progressive (crescentic) GN nclinically rapidly progressive GN, nvarious etiology (immune-complex mediated incl. IgA, pauci-immune + ANCA, anti-GMB) nsmall vessel vasculitis, SLE,… nnecrotising GN – capillary rupture, exudation – extracapillary proliferation - crescentic nImmunosuppression in active lesion + plasma exchange in known circulating AB (anti-GBM) nNo direct therapy in fibrosing lesion n Rapidly progressive (crescentic) GN RPGNSRPKY Rapidly progressive (crescentic) GN Fibrinoidní kapilární nekroza.jpg Anti-GBM disease nuncommon nrapidly progressive renal failure +/- hemoptysis (Goodpasture sy) nlinear deposits of IgG Glomerulopathy due to vascular disorders nin hypertension nrenal infarction nrenal artery stenosis nthrombotic microangiopathy (HUS, thrombotic thrompocytopenic purpura) nsystemic vasculitis (ANCA+, microscopic polyangiitis, anti-GBM GN) n Nephropathy in hypertension nBenign nephrosclerosis= compensated hypertension nmacro: decreased size, granulated surface, atrophic cortex 2-3 mm nmicro: hyaline insudation on arteriolar wall, arteries w. hypertrophic media, intimal sclerosis, glomerular ischemic changes + loss, tubular atrophy, interstitial fibrosis nwrinkling GBM Benign nephrosclerosis nefrosklerosa Benign nephrosclerosis arteriolosclerotic arteriolohylinosa DSCN1577 koradenomyacystygranpovrch Nephrosclerosis arterioarteriolo granulations and post-infarct scars arteriepřimalignínefrosklerose maligníhypertense Onion-skin formations – hyperplastic arteriolosclerosis +/- arteriolonecrosis; hyaline arteriolosclerosis hypertension Fibrinoid necrosis Nephrosclerosis ischermické změny glomerulů.jpg Nephropathy in hypertension nMalignant nephrosclerosis = accelerated hypertension (190/130 mm Hg) napprox. 5 % HT nemergency, radical antihypertensive th. necessary nhigh risk of RF, heart failure, brain haemorrhage nendothelial damage nmacro edema, pinpoint bleeding, infarctions nmicro edema, fibrinoid necrosis, possible thrombi, haemorrhagic necrosis or oschemic collapse of glomeruli n Nephropathy in hypertension Fibrinoidní nekroza arterioly.jpg Renal infarction nCauses of renal artery branches obstruction nthrombembolia; nthrombosis nvasculitis n aneurysm of abdominal aorta n n n n inarktledv inarktnarezu2 Renal artery stenosis ncause of renovascular hypertension n↓ of blood pressure in afferent arteriole nactivation of renin-angiotensin system → n↑ BP, atrophy in longer duration nhypertension in contralateral kidney n Benign nephrosclerosis – hypertensive nephropathy na. renalis stenosis, renal atrophy and hypertension (Goldblatt) asledvarterie Thrombotic microangiopathy nEndothelial damage → microthrombi → damage of erythocytes + platelets → hemolytic anaemia nfibrinoid necrosis without vasculitis nHemolytic-uremic sy (typical – epidemic – Shiga toxin; atypical – antiphospholipid antibodies, malignant hypertension, pregnancy, drugs, irradiation, = in complement dysregulation nThrombotic thrombocytopenic purpura ngenetic defficiency in von Willebrand-cleaving factor nacquired (AI, therapy) sudden, CNS, heart damage nPregnancy complications: pre- eclampsia n n Hemolytic-uremic syndrome 1)Ischemic cortical changes with tubular dilatation 2)Disperse focal hemoragies, necroses Acute nephropathy + haemolysis thrombocytopenia krovéhemoragiešoknekrosa korovánekrosa Hemolytic-uremic syndrome nMicrotrombi in glomerular capillaries (endothelial injury + platelet activation) nThickening of capillary walls nNecrosis and intimal hyperplasia of small arteries xxxxx Systemic vasculitis n3 main types nvasculitis directly caused by autoantibodies nanti-GBM glomerulonephritis – Goodpasture sy nimmune complex vasculitis nHenoch-Schönlein purpura nANCA vasculitis ngranulomatosisi w. polyangiitis (Wegener v.) c-ANCA nmicroscopic polyangiitis p-ANCA nChurg-Strauss eosinophilic granulomatosis w. polyangiitis n n Systemic vasculitis c-ANCA nSmall vessel vasculitis nIncidence ↑ with age nHigh mortality nRenal or multiorgan nRapidly progressive GN, hematuria, proteinuria, red cell casts Glomerulopathy in SLE nMultiorgan AI disease nVariable autoantibodies nKidney damage in 80 % nVariable presentation and/or type of kidney damage nasymptomatic hematuria + proteinuria nnephrotic sy nRPGN n6 classes of lupus nephritis n Lupus nephritis 15sleimf 11slegnhe 12slegnafog Glomerular cells proliferation Immune deposit (red) Deposits in direct immnofluorescence Chronic glomerulonephritis nend stage of variable glomerular disease ncommonly no more identifiable n different rate of progression in different diseases nFSGS 50-80% nRPGN, membranous, membranoproliferative ~ 50% npoststreptococcal 1-2% Chronic glomerulonephritis ngranular surface (!x chronic interstitial nephritis, nephrosclerosis, diabetic nephropathy,…) nthin cortex nobliterated glomeruli, arterio- and arteriolosclerosis (hypertension), tubular atrophy chrongn Chronic GN – end-stage kidney ChronsklerotisujíciGN Tubulo-interstitial disorders nConcurrent damage to the tubular epithelium and interstitium nUsually no glomerular damage, or only secondary (e.g. glomerulosclerosis) n Tubulo-interstitial disorders - groups nTUBULOINTERSTITIAL NEPHRITIS (TIN) n Acute pyelonephritis n Chronic pyelonephritis, reflux nephropathy n Abacterial interstitial nephritis (drugs, etc.) nISCHEMIC AND TOXIC INJURY n Acute tubular necrosis nOTHERS (e.g. obstructive uropathy, tbc, myeloma, urate nephropathy, immunologic reaction AI, posttransplant) Acute tubular necrosis (ATN) nDestruction/injury of tubular epithelium, leading to acute diminution or loss of renal function nIschemic ATN – due to decreased or interrupted blood flow, e.g. in shock, trauma, acute pancreatitis, polyarteritis nodosa, haemoglobinuria (haemolysis), myoglobinuria (crush), etc. nNephrotoxic ATN – direct toxic injury to the tubules by drugs, heavy metals (mercury), organic solvents (carbon tetrachloride), ethylene glycol Acute tubular necrosis (ATN) nMorphology: ischemic ATN with loss of proximal epithelial brush border, cell flattening, focal tubular epithelial necrosis along the whole nephron, BM rupture, occlusion by casts; interstitial oedema, inflammatory infiltrate nLater epithelial regeneration starting from uninjured parts nToxic ATN: extensive tubular necrosis/cytotoxic changes along the proximal tubules Acute tubular necrosis (ATN) ATNmikro ATNmikro2 Tubulointerstitial nephritis induced by drugs and toxins (hypersensitivity nephritis) nSulfonamids, synthetic penicilins, some diuretics, NSAIDs n7-15 days after exposure fever, eosinophilia, rash, hematuria, proteinuria, leukocyturia, cca 50% acute renal failure with oliguria nLate-phase reaction of an IgE-mediated hypersensitivity (type I) nOedema and mononuclear interstitial infiltration, commonly with eosinophils, giant cell granulomas may be present. Tubulitis and tubular regressive changes. Analgesic nephropathy nChronic renal disease due to excessive use of analgesic mixtures nForm of chronic tubulointerstitial nephritis with renal papillary necrosis nCombination effects of aspirin (papillary ischaemia), phenacetin (toxic metabolites) Renal TBC nPart of miliary spread nSolitary postprimary tbc lesion nGross: caseous-cavernous mass with fibrous capsule (closed tbc) or rupture and drain into pelvis (open tbc), possible infection of urinary tract. Renal TBC tbcledv Caseation kittniere copy Urate nephropathy nHyperuricemic disorders (urate crystals formation) may lead to 3 forms of injury: nAcute urate nephropathy in patients with haematologic malignancies, commonly during chemotherapy (extensive cell breakdown – release of nucleic acids – urate crystals in tubules – acute renal failure nChronic urate nephropathy – in gout. Urate crystals surrounded by foreign body giant cells, tubulo-interstitial nephritis nUrate stones Multiple myeloma nAmyloidosis nMyeloma nephrosis: tubular casts formed by precipitated Bence-Jones protein, nephrohydrosis giant cell reaction myelomováledvina Renal tumors n WHO histological classification of renal tumors nRenal cell tumours nMetanephric tumours nNephroblastic tumours nMesenchymal tumours nMixed mesenchymal and epithelial tumours nNeuroendocrine tumours nHaematopoietic and lymphoid tumours nGerm cell tumours nMetastatic tumours WHO classification of renal cell tumors nClear cell renal cell carcinoma nMultilocular cystic renal neoplasm of low malignant potential nPapillary renal cell carcinoma nHereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated renal cell carcinoma nChromophobe renal cell carcinoma nCollecting duct carcinoma nRenal medullary carcinoma nMiT Family translocation carcinomas nSuccinate dehydrogenase (SDH)-deficient renal carcinoma nMucinous tubular and spindle cell carcinoma nTubulocystic renal cell carcinoma nAcquired cystic disease associated renal cell carcinoma nClear cell papillary renal cell carcinoma nRenal cell carcinoma, unclassified nPapillary adenoma nOncocytoma n Benign renal tumors nCortical papillary adenoma n n nSmall tumors (1-15 mm), nMay be multiple nPapillary structure koradenomyacystygranpovrch Benign renal tumors nAngiomyolipoma (PEComa), mesenchymal angiomylipom Benign renal tumors nOncocytoma epithelial, asymptomatic onkocytom onkocytom2 onkocytom3 Renal cell carcinoma nAdenocarcinoma from tubular epithelium (clear cell - Grawitz ) n85% of renal malignancies caledviny RCC nClear cell (conventional) RCC (80%) nChromophobe RCC nPapillary RCC n nRisk f.: smoking, obesity, HT, genetic factors, industrial pollution, chemicals (asbestos, arsenic, organic diluents, ...) nIncidental finding, hematuria, metastasis Renal cell carcinoma n caledvinyX Renal cell carcinoma n caledvinyY Renal cell carcinoma n caledvinyQ Renal cell carcinoma caledvinyZ RCC nClear cell (conventional) RCC (80%) nglycogene + lipids in cytoplasm, common regressive changes, venous invasion, may have late metastasis nnuclear grading nChromophobe RCC 5 % nvery good prognosis, eosinophilic granular cytoplasm nPapillary RCC: 15 %, ncommonly multifocal / bilateral, stromal foam macrophages n Renal cell carcinoma caledvinyhistol Monosomia chromosom 1 (FISH) in chromophobe ca copy Transitional cell ca of the renal pelvis n capanvicky Transitional cell ca of the renal pelvis n capanvicky2 capanvicky3 Wilms’ tumor - nephroblastoma nMalignant embryonal tu metanefrogenous blastema nPeak incidence 1-4 yrs n3rd most common ch. malignancy, treatable nhematuria, local compression nSuppresoric gene WT1 (11p13), WT2 (11p15) nMACRO: large, soft nMICRO blastic cells, immature epithelial, mesenchymal differentiation wilmshistol tuledv wilms Wilms’ tumor - nephroblastoma n 40x Secondary tumors nLocal spread (adrenals, pancreas, liver) nLung carcinoma nMalignant lymphoma nOthers n